Salmonella Outer Protein B Suppresses Colitis Development via Protecting Cell From Necroptosis.

Salmonella effectors translocated into epithelial cells contribute to the pathogenesis of infection. They mediate epithelial cell invasion and subsequent intracellular replication. However, their functions in vivo have not been well-identified. In this study, we uncovered a role for Salmonella outer protein B (SopB) in modulating necroptosis to facilitate bacteria escape epithelial cell and spread to systemic sites through a Salmonella-induced colitis model. Mice infected with SopB deleted strain ΔsopB displayed increased severity to colitis, reduced mucin expression and increased bacterial translocation. In vitro study, we found there was an increased goblet cell necroptosis following ΔsopB infection. Consistently, mice infected with ΔsopB had a strong upregulation of mixed lineage kinase domain-like (MLKL) phosphorylation. Deletion of MLKL rescued severity of tissue inflammatory, improved mucin2 expression and abolished the increased bacterial translocation in mice infected with ΔsopB. Intriguingly, the expression of sopB in LS174T cells was downregulated. The temporally regulated SopB expression potentially switched the role from epithelial cell invasion to bacterial transmission. Collectively, these results indicated a role for SopB in modulating the onset of necroptosis to increased bacteria pathogenesis and translocated to systemic sites.

MLKL deficiency inhibits DSS-induced colitis independent of intestinal microbiota.

The maintenance of intestinal tissue homeostasis is vital for the resistance against inflammatory bowel diseases (IBDs). Necroptosis is identified as an alternative mode of regulated cell death, which plays a pivotal role in tissue homeostasis. Thus, the roles of RIP3-mediated necroptosis in intestinal inflammation have been extensively studied. However, the biological implications of the mixed lineage kinase-like protein (MLKL), a molecule downstream of RIP3 in gut remain unclear. In this study, the role of MLKL in DSS-induced colitis was examined, and the contribution of gut microbiota was also determined. Compared with non-littermate WT mice, the survival rate, clinical score, intestinal damage and intestinal mucosal barrier integrity of non-littermate MLKL-deficient mice are significantly improved. MLKL deficiency prevents inflammatory cytokines production and MAPK signaling activation. Hence, MLKL deficiency inhibits DSS-induced colitis. Moreover, we proved that DSS susceptibility difference between two genotypes is not driven by intestinal microbiota based on the co-housing of two non-littermate genotypes and qPCR detection of fecal dominant bacterial taxa.

Non-Hematopoietic MLKL Protects Against Salmonella Mucosal Infection by Enhancing Inflammasome Activation.

The intestinal mucosal barrier is critical for host defense against pathogens infection. Here, we demonstrate that the mixed lineage kinase-like protein (MLKL), a necroptosis effector, promotes intestinal epithelial barrier function by enhancing inflammasome activation. MLKL-/- mice were more susceptible to Salmonella infection compared with wild-type counterparts, with higher mortality rates, increased body weight loss, exacerbated intestinal inflammation, more bacterial colonization, and severe epithelial barrier disruption. MLKL deficiency promoted early epithelial colonization of Salmonella prior to developing apparent intestinal pathology. Active MLKL was predominantly expressed in crypt epithelial cells, and experiments using bone marrow chimeras found that the protective effects of MLKL were dependent on its expression in non-hematopoietic cells. Intestinal mucosa of MLKL-/- mice had impaired caspase-1 and gasdermin D cleavages and decreased interleukin (IL)-18 release. Moreover, administration of exogenous recombinant IL-18 rescued the phenotype of increased bacterial colonization in MLKL-/- mice. Thus, our results uncover the role of MLKL in enhancing inflammasome activation in intestinal epithelial cells to inhibit early bacterial colonization.

Dehydration of fructose to 5-hydroxymethylfurfural by rare earth metal trifluoromethanesulfonates in organic solvents.

The catalytic dehydration of fructose to 5-hydroxymethylfurfural (HMF) was investigated by using various rare earth metal trifluoromethanesulfonates, that is, Yb(OTf)(3), Sc(OTf)(3), Ho(OTf)(3), Sm(OTf)(3), Nd(OTf)(3) as catalysts in DMSO. It is found that the catalytic activity increases with decreasing ionic radius of rare earth metal cations. Among the examined catalysts, Sc(OTf)(3) exhibits the highest catalytic activity. Fructose conversion of 100% and a HMF yield of 83.3% are obtained at 120°C after 2h by using Sc(OTf)(3) as the catalyst. Moreover, the catalytic dehydration of fructose was also carried out in different solvents, for example, DMA, 1,4-dioxane, and a mixture of PEG-400 and water. The results show that among the solvents DMSO is the most efficient in promoting the dehydration of fructose to HMF, and no rehydration byproducts such as levulinic acid and formic acid are detected.

[Analysis of features for suicide attempters at emergency departments in general hospitals].

OBJECTIVE: To investigate the prevalence of various mental disorders of suicide attempters and analyze the clinical features of suicide attempters with mental disorders. METHODS: The investigators randomly selected four Class III general hospitals from different parts of Shenyang and collected 239 suicide attempters over 15 years old at emergency room. When the conditions of suicide attempters improved after rescue, the investigators studied by suicide general table, self-injury questionnaire, Hamilton Depression Rating Scale for Depression-24 and Structure Clinical Interview for DSM-IV Axis I Disorders-Patient Edition. RESULTS: The overall prevalence of mental disorders in attempted suicides was 69.46% while self-injury, one of the highest prevalent mood disorders, accounted for 48.12%. During the year before suicide, only 7.23% of the suicide attempters with mental disorders consulted a psychologist or psychiatrist, and took anti-psychosis drugs, anti-depression or anti-anxiety drugs. Suicide attempters with mental disorders often committed suicide less impulsively. And their purpose was to relieve themselves and reduce the burden of others so that the rate of self-help was lower after their injuries occurred; suicide attempters with mental disorders had more obvious symptoms. And their degrees of depression were greater (P < 0.05) than ones without mental disorders. CONCLUSION: The prevalence of mental disorders at emergency rooms in general hospitals is high in suicide attempts, but the pre-suicide consulting rate remains so low. The depressive components of mental disorders are most directly related to suicidal behaviors of suicide attempters.